Subjective and psychophysical olfactory and gustatory dysfunction among COVID-19 outpatients; short- and long-term results

Background Olfactory and gustatory dysfunctions are early symptoms of SARS-CoV-2 infection. Between 20–80% of infected individuals report subjective altered sense of smell and/or taste during infection. Up to 2/3 of previously infected experience persistent olfactory and/or gustatory dysfunction after 6 months. The aim of this study was to examine subjective and psychophysical olfactory and gustatory function in non-hospitalized individuals with acute COVID-19 up to 6 months after infection. Methods Individuals aged 18-80-years with a positive SARS-CoV-2 PCR test no older than 10 days, were eligible. Only individuals able to visit the outpatient examination facilities were included. Gustatory function was tested with the Burgharts Taste Strips and olfactory function was examined with the Brief Smell Identifications test (Danish version). Subjective symptoms were examined through an online questionnaire at inclusion, day 30, 90 and 180 after inclusion. Results Fifty-eight SARS-CoV-2 positive and 56 negative controls were included. 58.6% (34/58) of SARS-CoV-2 positive individuals vs. 8.9% (5/56) of negative controls reported subjective olfactory dysfunction at inclusion. For gustatory dysfunction, 46.5% (27/58) of positive individuals reported impairment compared to 8.9% (5/56) of negative controls. In psychophysical tests, 75.9% (46/58) had olfactory dysfunction and 43.1% (25/58) had gustatory dysfunction among the SARS-CoV-2 positive individuals at inclusion. Compared to negative controls, SARS-CoV-2 infected had significantly reduced olfaction and gustation. Previously infected individuals continued to report lower subjective sense of smell 30 days after inclusion, whereafter the difference between the groups diminished. However, after 180 days, 20.7% (12/58) positive individuals still reported reduced sense of smell and taste. Conclusion Olfactory and gustatory dysfunctions are prevalent symptoms of SARS-CoV-2 infection, but there is inconsistency between subjective reporting and psychophysical test assessment of especially olfaction. Most individuals regain normal function after 30 days, but approximately 20% report persistent olfactory and gustatory dysfunction 6 months after infection.


4)
Lines 95 and 96 -The authors state that the taste test -Burghart's Taste Stips and the olfactory test -Brief Smell 97 Identification Test are objective tests that were performed by an otolaryngologist. However, these tests are not objective, but subjective/psychophysical, as they depend on the individual's response. The only objective olfactory test is the event-related Olfactory Evoked Potential and the Electroolfactogram, which were not performed in the present sample.
5) Line 95 -How are these tests evaluated for normality and degrees of olfactory and gustatory loss? There is no description for the reader throughout the article.
6) Line 99 -No objective, gustatory or olfactory test was performed in this study. I recommend removing that phrase.
7) Line 107 -The authors state that a questionnaire was made to obtain demographic data and questions 1-6 of the SNOT-22 questionnaire were added. Why didn't you complete the SNOT-22 questionnaire, as it is validated and used internationally? It would be interesting and important to have carried out a complete assessment of the quality of life of each participant during the study period. 8) Line 109 -All participants answered this modified questionnaire four times during the study: at baseline, 30, 60, and 90 days? Is it possible to trust that these questionnaires were actually answered at these times since they were sent by e-mail? Were the psychophysical tests redone 30, 60, and 90 days after the first assessment? Or at least at the end of the study? This is not clear from the text.

Statistical methods
9) Line 112 -There are no objective methods for the assessment of smell and taste in this study.
10) Line 113 -The BSIT test is not objective, it is psychophysical.

11)
Lines 122 to 127 -I suggest putting this data in a table and drawing attention in writing only to the most important result.
12) Line 128 -The authors have already put in the title of the table what is being exposed here. I recommend removing and adding the caption.
13) In table 1it is necessary to place a legend below the table, for the acronyms PCR, OD, and GD and for other information that is necessary for the understanding of the table.
14) In table 1, in the "Reported symptoms and risk factors of OD/GD" part, add the symbol of (n) for the total number of participants and (%) to identify that the data are being presented in percentage.
15) In table 1, in the "Objective assessment" part, I suggest putting "ENT assessment" and also indicating that the data are presented as a percentage.
16) Line 134 -The acronym IQR is cited for the first time, but there is no full description of -Inter Quartile Range. This description will only occur on line 154.

Olfactory dysfunction
17) Lines 131 to 141 -There is no need to write down all the data that is already presented in the  Discussion 26) Line 181 -Replace "objective tests" with "psychophysical tests".
27) Lines 181 to 185 -It is interesting to start the discussion by stating the main and most important result of the study. The description presented in this paragraph has already been done in the methodology.
28) Line 194 -"(…) suggesting that some individuals fail to recognize their OD." This is important to point out, as many individuals cannot have a clear perception of how the sense of smell is.

29)
In the discussion also review the description of what are subjective and objective tests, because as already mentioned above, all tests performed by the doctor were psychophysical and not objective. The previous questionnaire applied for the selection of participants is a self-report of olfaction.
30) Do not put so many results, as these are already in the tables. Discuss them only and focus only on the most important ones. Discussion is the crucial part to discuss the study data with what there is already literature.

31)
The authors report important limitations, mainly the bias in filling out the initial questionnaire.
Conclusion 32) Do not put statistical data in the conclusion. And do not summarize the study in this part.
33) The conclusion should be brief and answer your research question/objective. Do not put information that has already been discussed in the article or that is in the methodology. 34) Objective: "This study aimed to examine subjective and objective olfactory and gustatory function in non hospitalized individuals with acute COVID-19 up to 6 months after infection." Answer in the conclusion: Was there an improvement in olfactory and gustatory function, after 6 months of the initial diagnosis of COVID? 35) Recommendation: send the article to be reviewed by a native speaker of English.